Photosensitized Singlet Oxygen Research Articles

Synthesis of novel π-extended D–A–D-type dipyrido[3,2-a:2′,3′-c]phenazine derivatives and their photosensitized singlet oxygen generation

Electron donor–acceptor–donor (D–A–D) π-conjugated molecules based on dipyrido[3,2-a:2′,3′-c]phenazine (dppz) were developed as photosensitizers for singlet oxygen generation.

Self-assembly of a symmetrical dimethoxyphenyl substituted Zn(II) phthalocyanine into nanoparticles with enhanced NIR absorbance for singlet oxygen generation

Phthalocyanine (Pc) molecules have been investigated as photosensitizers (PS) for singlet oxygen (1O2) generation because of their intense absorption bands in the near-infrared region, which is desirable for applications such as photodynamic therapy (PDT). Here, we have designed a sterically crowded symmetrical Zn(II) phthalocyanine (PC-1), which contains 8 dimethoxyphenyl substituents, and studied its optical properties. PC-1 exhibits good thermal stability, appropriate theoretical HOMO and LUMO energy levels and band gap which are suitable for optoelectronic applications. PC-1 was converted into hydrophilic nanoparticles (PC-1NPs) via a solvent exchange based self-assembly approach, which exhibited good water dispersability, as well as uniform morphology and size. Optical studies revealed a bathochromic-shift in absorbance in the NIR wavelength region and 1O2 generation. These results suggest that PC-1 phthalocyanine is a potential candidate for photoinduced oxidative processes in biological and catalytic applications.

Hitting Two Molecules with One Photon; Photooxidation of C60 By Self-Sensitized Singlet Oxygen

Thanks to its unique properties, C60 has remarkably impacted nanoscience in the past two decades. Specifically, it is the most efficient singlet oxygen (1O2) photosensitizer ever known. Yet, there has been no reported evidence of 1O2 reacting with its original C60 photosensitizer, which we refer to as ‘oxidation with self-sensitized 1O2’. The literature suggests both oxygen and C60 must be at excited states to undergo reaction, implying a 2-photon process: first, oxygen is photosensitized in the C60 and O2 complex (1C60·1O2); second, 1C60* is photogenerated (1C60*·1O2). However, this scheme is unlikely to occur in a solvent, where 1O2 would be rapidly quenched by solvent molecules before the second photon is absorbed by C60. Here, we substantiate a single-photon oxidation mechanism via self-sensitized 1O2 in solvents above a photon energy of 3.7 eV. Using phosphorescence (1270 nm) excitation spectroscopy and kinetics measurements, we identify the transition, 1Ag → 21Hu, as the driver of photooxidation. Subsequently, intersystem crossing generates the higher energy triplet transient, 3C60**·3O2, which then converts to 1C60*·1O2. Both excited by the same photon, at the same place and same time, C60 and O2 readily react. Such triplet-triplet annihilation, yielding two simultaneously-excited singlets, is unique. This scheme is stimulating for the conception of novel efficient photochemical processes, implemented with C60 or other photosensitizers. Additionally, rate constants derived from this study allow us to predict a C60 half-life of about a minute in the atmosphere, possibly explaining the scarceness of C60 in the environment.

Double-Stranded DNA Matrix for Photosensitization Switching

Photosensitization, originated from the activation of triplet states, is the basis of many photodynamic applications, but often competes with a series of nonradiative processes. Herein, we communic...

Minimizing the Electron Donor Size of Donor–Acceptor-Type Photosensitizer: Twisted Intramolecular Charge-Transfer-Induced Triplet State and Singlet Oxygen Formation

Efficient and selective heavy atom-free singlet oxygen photosensitizers (HAFPS) are highly desirable for chemistry, pharmaceutical sciences, phototherapy, and environmental sciences. The donor–acce...

Triply pH-activatable porphyrin as a candidate photosensitizer for near-infrared photodynamic therapy and diagnosis

To achieve highly selective tumor therapy and diagnosis, we have developed a novel low-pH-activatable photosensitizer, AI4P, which is a porphyrin derivative possessing four 5-diethylaminoindole units. These 5-diethylaminoindole units enhance internal conversion from the first excited singlet state to suppress fluorescence and photosensitization of singlet oxygen. Upon decreasing pH, AI4P becomes protonated form. This protonated form exhibited strong absorption at 740 nm, which is the optimal wavelength for light penetration through living tissues. In addition, the protonated form exhibited efficient fluorescence and photosensitization. Therefore, AI4P is proposed as a triply activatable near-infrared photosensitizer that can activate near-infrared absorption, fluorescence, and photosensitization simultaneously. The activation ratio was over 200, which represents almost complete activation.

Multi-scale simulation reveals that an amino acid substitution increases photosensitizing reaction inputs in Rhodopsins.

Evaluating the availability of molecular oxygen (O2 ) and energy of excited states in the retinal binding site of rhodopsin is a crucial challenging first step to understand photosensitizing reactions in wild-type (WT) and mutant rhodopsins by absorbing visible light. In the present work, energies of the ground and excited states related to 11-cis-retinal and the O2 accessibility to the β-ionone ring are evaluated inside WT and human M207R mutant rhodopsins. Putative O2 pathways within rhodopsins are identified by using molecular dynamics simulations, Voronoi-diagram analysis, and implicit ligand sampling while retinal energetic properties are investigated through density functional theory, and quantum mechanical/molecular mechanical methods. Here, the predictions reveal that an amino acid substitution can lead to enough energy and O2 accessibility in the core hosting retinal of mutant rhodopsins to favor the photosensitized singlet oxygen generation, which can be useful in understanding retinal degeneration mechanisms and in designing blue-lighting-absorbing proteic photosensitizers.

An integrated photosensitizing/adsorbent material for the removal of triclosan from water samples

Triclosan, a recalcitrant micropollutant linked to antimicrobial resistance, is not completely eliminated during wastewater treatment, reason why it has become ubiquitous, causing serious environmental problems. Photocatalytic removal of triclosan has been investigated using sunlight and a composite material consisting of tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) chloride [Ru(dip)3]Cl2 –a singlet oxygen (1O2) photosensitizer– immobilized on poly-dimethylsiloxane (PDMS) membranes. The efficiency of triclosan photodegradation has been evaluated, as well as the influence of variables such as pH, water matrix composition and triclosan adsorption on the material.The sunlight-driven process led to an effective decrease in triclosan concentration (C0 as high as 0.35 or 1.5 mg L−1 in ultra-pure and natural water samples, respectively), with removal rates > 80% within 30 min in the presence of the photosensitizing material, while it was ≤ 50% in direct photolysis tests in the absence of the material. The improved efficiency of triclosan removal with the photosensitizing material is even more effective with the phenolic form of triclosan, which may be attributed to synergistic adsorption of the pollutant on the polymer matrix and subsequent photodegradation by 1O2. Direct photolysis is, however, the dominant pathway for the depletion of the phenolate form, although the reaction with 1O2 always increases the removal rates of the deprotonated triclosan, due to the strong electrophilic nature of this reactive oxygen species.LC-QTOF-MS screening of treated water samples did not show the presence of ions characteristic of already reported toxic triclosan phototransformation products (e.g. dioxins, dichlorophenols, etc). Moreover, these photosensitizing/adsorbent materials can be easily incorporated into solar photoreactors, allowing simple separation of the treated water. Therefore, these integrated photosensitizing/adsorbent materials may offer novel green and cost-effective options for sustainable treatment of polluted waters.

Unusual Oxidative Dealkylation Strategy toward Functionalized Phenalenones as Singlet Oxygen Photosensitizers and Photophysical Studies.

A series of functionalized 6-alkoxy phenalenones was prepared through an unprecedented oxidative dealkylation of readily available phenalene precursors. The starting phenalenes were efficiently synthesized via an aminocatalyzed annulation/O-alkylation strategy starting from simple substrates. The spectroscopic properties of some phenalenones were investigated in different solvents. Introducing an alkoxy substituent at the 6-position onto the phenalenone framework results in a red shift of the absorption. The synthesized phenalenones exhibit low fluorescence quantum yields, and the fluorescence decay was studied in different solvents, highlighting the presence of several lifetimes. The singlet oxygen (1O2) photosensitizing propensity of some phenalenones was investigated, and the results showed the striking importance of the phenalenone molecular structure in generating singlet oxygen with high yields. The ability of phenalenones to generate singlet oxygen was then harnessed in three photooxygenation reactions: anthracene oxidation, oxy-functionalization of citronellol through the Schenck-ene reaction, and photooxidation of a diene.

Suppression of menthyl anthranilate (UV-A sunscreen)-sensitized singlet oxygen generation by Trolox and , α-tocopherol

Menthyl anthranilate (MA, tradename meradimate) is a UV-A absorber. The interactions of ground-state molecular oxygen with the long-lived triplet state of MA produce singlet oxygen through energy transfer. The quantum yield of singlet oxygen generation is 0.12 in air-saturated ethanol. Kinetic traces of the near-IR phosphorescence of singlet oxygen generated by MA-photosensitization have been measured in the absence and presence of Trolox (a water-soluble analogue of vitamin E and a quencher of singlet oxygen) and α-tocopherol (vitamin E, a natural antioxidant) in ethanol. Fluorescence and transient absorption measurements suggest that Trolox and α-tocopherol quench the lowest excited singlet and triplet states of MA. As a result, Trolox and α-tocopherol suppress MA-photosensitized singlet oxygen generation. Not only the quenching of singlet oxygen but also the suppression of singlet oxygen generation is the mechanism of antioxidant properties of Trolox and α-tocopherol for MA. The ability of α-tocopherol to suppress the MA-photosensitized singlet oxygen generation in isododecane, used as a solvent for an oil-soluble UV absorber, is close to that in ethanol. Suppression of sunscreen-photosensitized singlet oxygen generation is an important method for the formulation of safe cosmetic sunscreens.

Single-photon oxidation of C60 by self-sensitized singlet oxygen

C60 is regarded as the most efficient singlet oxygen (1O2) photosensitizer. Yet, its oxidation by self-sensitized 1O2 remains unclear. The literature hints both oxygen and C60 must be at excited states to react, implying a two-photon process: first, oxygen is photosensitized (1C60•1O2); second, C60 is photoexcited (1{mathrm{C}}_{60}^{ast}•1O2). However, this scheme is not plausible in a solvent, which would quench 1O2 rapidly before the second photon is absorbed. Here, we uncover a single-photon oxidation mechanism via self-sensitized 1O2 in solvents above an excitation energy of 3.7 eV. Using excitation spectroscopies and kinetics analysis, we deduce photoexcitation of a higher energy transient, 3{mathrm{C}}_{60}^{{ast}{ast}}•3O2, converting to 1{mathrm{C}}_{60}^{ast}•1O2. Such triplet-triplet annihilation, yielding two simultaneously-excited singlets, is unique. Additionally, rate constants derived from this study allow us to predict a C60 half-life of about a minute in the atmosphere, possibly explaining the scarceness of C60 in the environment.

Room-Temperature Phosphorescence and Efficient Singlet Oxygen Production by Cyclometalated Pt(II) Complexes with Aromatic Alkynyl Ligands.

The synthesis of five novel cyclometalated platinum(II) compounds containing five different alkynyl-chromophores was achieved by the reaction of the previously synthesized Pt-Cl cyclometalated compound (1) with the corresponding RC≡CH by a Sonogashira reaction. It was observed that the spectral and photophysical characteristics of the cyclometalated platinum(II) complexes (Pt-Ar) are essentially associated with the platinum-cyclometalated unit. Room-temperature emission of the Pt-Ar complexes was attributed to phosphorescence in agreement with DFT calculations. Broad nanosecond (ns)-transient absorption spectra were observed with decays approximately identical to those obtained from the emission of the triplet state. From the femtosecond-transient absorption (fs-TA) data, two main excited-state decay components were identified: one in the order of a few picoseconds was assigned to fast intersystem crossing to populate the triplet excited-state and the second (hundreds of ns) was associated with the decay of the transient triplet state. In general, efficient singlet oxygen photosensitization quantum yields were observed from the triplet state of these complexes.

Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT.

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low-toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.

Phosphorous tetrabenzocorrolazine from its metal-free phthalocyanine precursor: Its facile synthesis, high fluorescence emission, efficient singlet oxygen formation, and promising hole transporting material

We have synthesized tetra(4-tert-butyl phenoxy)-tetrabenzocorrolazine phosphorous POTBC(β-OPB)4, a functional π-conjugated macrocycle compound derived from corrole or corrolazine, by a one step procedure from its metal free phthalocyanine precursor. The product structure is characterized by UV–Vis absorption, MS, NMR and IR spectral methods. We have also studied their fluorescence properties, excited triplet state formation, photosensitized singlet oxygen production, and their application as undoped hole transporting layer (HTL) in perovskite solar cells (PSC). The results show that POTBC(β-OPB)4 is highly emissive (fluorescence quantum yield 0.60 in the red region which is little affected by solvent), it also exhibits significant singlet oxygen formation ability (quantum yield 0.40 which is little influenced by solvent), and show remarkable power conversion efficiency (15.8%) as undoped HTL. These facts suggest that POTBC(β-OPB)4 is a promising fluorescence imaging agent and good singlet oxygen photosensitizer for photodynamic therapy of tumor. It is also a good candidate as undoped hole transporting material for PSC.

PH-Dependent photodynamic activity of bis(6-methyl-3-pyridylmethoxy)P(V)tetrakis(p-methoxyphenyl)porphyrin

To control the photodynamic activity of a porphyrin photosensitizer, an electron-donor-connecting porphyrin P(V) complex, bis(6-methyl-3-pyridylmethoxy)P(V)tetrakis(p-methoxyphenyl)porphyrin (PyrP(V)TMPP), was synthesized. The fluorescence lifetime measurement demonstrated that the photoexcited PyrP(V)TMPP is quenched through intramolecular electron transfer and this quenching is suppressed by protonation of the pyridyl moiety, an electron donor. The pKa value of protonated PyrP(V)TMPP was about 7, and the quantum yields of photosensitized singlet oxygen (1O2) generation and oxidation of nicotinamide adenine dinucleotide through 1O2 generation and electron transfer mechanisms were increased under acidic condition. In addition, a hydrophobic environment of protein activated PyrP(V)TMPP to photosensitize protein damage.

Assessing Amphiphilic ABAB Zn(II) Phthalocyanines with Enhanced Photosensitization Abilities in In Vitro Photodynamic Therapy Studies Against Cancer.

We have previously demonstrated that singlet oxygen photosensitization abilities of Zn(II) phthalocyanines (Zn(II)Pcs) are enhanced through α-functionalization with bulky fluorinated substituents (i.e., bis(trifluoromethyl)phenyl units) at facing positions of ABAB Zn(II)Pcs, where A and B refer to differently functionalized isoindoles. In this work, we have prepared the Zn(II)Pc ABAB 1 endowed with hydrophilic triethylene glycol monomethyl ether (i.e., at the A isoindoles) to provide solubility in aqueous media, together with its A3B and A4 counterparts, and compared their ability to behave as photosensitizers for photodynamic therapy. All photophysical data, aggregation studies and preliminary in vitro biological assays in cell cultures of SCC-13 (squamous cell carcinoma) and HeLa (cervical cancer cells), have proved ABAB 1 as the best photosensitizer of the series.

Correction: Substrate and product binding inside a stimuli-responsive coordination cage acting as a singlet oxygen photosensitizer.

Correction for 'Substrate and product binding inside a stimuli-responsive coordination cage acting as a singlet oxygen photosensitizer' by Sonja Pullen et al., Dalton Trans., 2020, 49, 9404-9410, DOI: 10.1039/D0DT01674H.

Substrate and product binding inside a stimuli-responsive coordination cage acting as a singlet oxygen photosensitizer.

An acridone-based, interpenetrated double cage [3BF4Pd4L8] acts as a photosensitizer for generating singlet oxygen which adds to 1,3-cyclohexadiene in a [2+4] hetero-Diels-Alder reaction to form 2,3-dioxabicyclo[2.2.2]oct-5-ene. Photocatalytic activity was exclusively observed for the assembled cage, whereas the free organic ligand L decomposes upon irradiation. While cage [3BF4Pd4L8] does not accept any organic guests, NMR, MS and single crystal X-ray results reveal that both substrate and product are readily encapsulated in the central pocket of its chloride-activated form [2Cl@Pd4L8]. The system combines multiple functions (photosensitization, allosteric activation and guest uptake) within a structurally complex, mechanically-bound self-assembly built up from a simple and readily accessible ligand.

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands.

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands was studied. Ru(ii) polypyridine complexes containing a di-fluorinated dppz (dipyrido[3,2-a:2′,3′-c]phenazine) or mono-trifluoromethylated dppz bidentate ligand and four pyridine monodentate ligands (complexes 3 and 4) were found to show potent photoactivated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Escherichia coli (E. coli) in both normoxic and hypoxic conditions. The bactericidal effect of complexes 3 and 4 under hypoxic conditions may stem from the fluorine-containing Ru(ii) aqua species after photo-induced pyridine dissociation, and DNA may be the potential antibacterial target. Photosensitized singlet oxygen may also account for their antibacterial activity under normoxic conditions. Moreover, negligible hemolysis rates as well as low dark- and photo-cytotoxicity toward human normal liver cells (L-O2) were also observed for both complexes. Our work may provide new insights into the development of novel and efficient Ru(ii) complex based photoactivatable antibacterial agents against antibiotic-resistant bacteria.

Understanding and controlling the efficiency of Au24M(SR)18 nanoclusters as singlet-oxygen photosensitizers.

Singlet oxygen, 1O2, can be generated by molecules that upon photoexcitation enable the 3O2 → 1O2 transition. We used a series of atomically precise Au24M(SR)18 clusters, with different R groups and doping metal atoms M. Upon nanosecond photoexcitation of the cluster, 1O2 was efficiently generated. Detection was carried out by time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The resulting TREPR transient yielded the 1O2 lifetime as a function of the nature of the cluster. We found that: these clusters indeed generate 1O2 by forming a triplet state; a more positive oxidation potential of the molecular cluster corresponds to a longer 1O2 lifetime; proper design of the cluster yields results analogous to those of a well-known reference photosensitizer, although more effectively. Comprehensive kinetic analysis provided important insights into the mechanism and driving-force dependence of the quenching of 1O2 by gold nanoclusters. Understanding on a molecular basis why these molecules may perform so well in 1O2 photosensitization is instrumental to controlling their performance.